Institution
European Chemicals Agency
About: European Chemicals Agency is a based out in . It is known for research contribution in the topics: European union & Risk assessment. The organization has 79 authors who have published 116 publications receiving 2788 citations. The organization is also known as: ECHA.
Papers
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TL;DR: A sensitive monitoring of contaminants in food and environment, such as chemical compounds, toxins and pathogens, is essential to assess and avoid risks for both, human and environmental health, and there is a high need for sensitive, robust and cost-effective biosensors that make real time and in situ monitoring possible.
262 citations
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University of Dundee1, Syngenta2, United States Environmental Protection Agency3, Dow Chemical Company4, Bayer5, European Chemicals Agency6, Auburn University7, Life Technologies8, Michigan State University9, Center for Drug Evaluation and Research10, Pennsylvania State University11, University of Pittsburgh12, University of Surrey13
TL;DR: The MOA for PB-induced rodent liver tumor formation was considered to be qualitatively not plausible for humans, supported by data from a number of epidemiological studies conducted in human populations chronically exposed to PB in which there is no clear evidence for increased liver tumor risk.
Abstract: The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are important nuclear receptors involved in the regulation of cellular responses from exposure to many xenobiotics and various physiological processes. Phenobarbital (PB) is a non-genotoxic indirect CAR activator, which induces cytochrome P450 (CYP) and other xenobiotic metabolizing enzymes and is known to produce liver foci/tumors in mice and rats. From literature data, a mode of action (MOA) for PB-induced rodent liver tumor formation was developed. A MOA for PXR activators was not established owing to a lack of suitable data. The key events in the PB-induced liver tumor MOA comprise activation of CAR followed by altered gene expression specific to CAR activation, increased cell proliferation, formation of altered hepatic foci and ultimately the development of liver tumors. Associative events in the MOA include altered epigenetic changes, induction of hepatic CYP2B enzymes, liver hypertrophy and decreased apoptosis; with inhibition of gap junctional intercellular communication being an associative event or modulating factor. The MOA was evaluated using the modified Bradford Hill criteria for causality and other possible MOAs were excluded. While PB produces liver tumors in rodents, important species differences were identified including a lack of cell proliferation in cultured human hepatocytes. The MOA for PB-induced rodent liver tumor formation was considered to be qualitatively not plausible for humans. This conclusion is supported by data from a number of epidemiological studies conducted in human populations chronically exposed to PB in which there is no clear evidence for increased liver tumor risk.
214 citations
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TL;DR: The World Health Organization/International Programme on Chemical Safety mode of action/human relevance framework has been updated to reflect the experience acquired in its application and extend its utility to emerging areas in toxicity testing and non‐testing methods.
Abstract: The World Health Organization/International Programme on Chemical Safety mode of action/human relevance framework has been updated to reflect the experience acquired in its application and extend its utility to emerging areas in toxicity testing and non-testing methods. The underlying principles have not changed, but the framework's scope has been extended to enable integration of information at different levels of biological organization and reflect evolving experience in a much broader range of potential applications. Mode of action/species concordance analysis can also inform hypothesis-based data generation and research priorities in support of risk assessment. The modified framework is incorporated within a roadmap, with feedback loops encouraging continuous refinement of fit-for-purpose testing strategies and risk assessment. Important in this construct is consideration of dose-response relationships and species concordance analysis in weight of evidence. The modified Bradford Hill considerations have been updated and additionally articulated to reflect increasing experience in application for cases where the toxicological outcome of chemical exposure is known. The modified framework can be used as originally intended, where the toxicological effects of chemical exposure are known, or in hypothesizing effects resulting from chemical exposure, using information on putative key events in established modes of action from appropriate in vitro or in silico systems and other lines of evidence. This modified mode of action framework and accompanying roadmap and case examples are expected to contribute to improving transparency in explicitly addressing weight of evidence considerations in mode of action/species concordance analysis based on both conventional data sources and evolving methods.
214 citations
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University of California, Berkeley1, University of Texas at El Paso2, University of California, Los Angeles3, Purdue University4, National Institute of Chemical Physics and Biophysics5, Fraunhofer Society6, Research Triangle Park7, University of Girona8, Spanish National Research Council9, Swiss Federal Institute of Aquatic Science and Technology10, ETH Zurich11, European Chemicals Agency12, Duke University13, Heriot-Watt University14, United States Environmental Protection Agency15, DuPont16, Ca' Foscari University of Venice17, Brown University18, University of Illinois at Urbana–Champaign19, National Institute of Standards and Technology20, GlobalFoundries21, Environment Canada22, Arizona State University23, Connecticut Agricultural Experiment Station24, University of Massachusetts Amherst25
TL;DR: Environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia.
Abstract: Engineered nanomaterials (ENMs) are increasingly entering the environment with uncertain consequences including potential ecological effects Various research communities view differently whether ecotoxicological testing of ENMs should be conducted using environmentally relevant concentrations-where observing outcomes is difficult-versus higher ENM doses, where responses are observable What exposure conditions are typically used in assessing ENM hazards to populations? What conditions are used to test ecosystem-scale hazards? What is known regarding actual ENMs in the environment, via measurements or modeling simulations? How should exposure conditions, ENM transformation, dose, and body burden be used in interpreting biological and computational findings for assessing risks? These questions were addressed in the context of this critical review As a result, three main recommendations emerged First, researchers should improve ecotoxicology of ENMs by choosing test end points, duration, and study conditions-including ENM test concentrations-that align with realistic exposure scenarios Second, testing should proceed via tiers with iterative feedback that informs experiments at other levels of biological organization Finally, environmental realism in ENM hazard assessments should involve greater coordination among ENM quantitative analysts, exposure modelers, and ecotoxicologists, across government, industry, and academia
194 citations
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TL;DR: This article offers a simple, pragmatic and justifiable approach for use within retrospective and prospective risk assessment of bioavailability within retrospective risk assessment frameworks for organic chemicals.
Abstract: The bioavailability of organic chemicals in soil and sediment is an important area of scientific investigation for environmental scientists, although this area of study remains only partially recognized by regulators and industries working in the environmental sector. Regulators have recently started to consider bioavailability within retrospective risk assessment frameworks for organic chemicals; by doing so, realistic decision-making with regard to polluted environments can be achieved, rather than relying on the traditional approach of using total-extractable concentrations. However, implementation remains difficult because scientific developments on bioavailability are not always translated into ready-to-use approaches for regulators. Similarly, bioavailability remains largely unexplored within prospective regulatory frameworks that address the approval and regulation of organic chemicals. This article discusses bioavailability concepts and methods, as well as possible pathways for the implementation of bioavailability into risk assessment and regulation; in addition, this article offers a simple, pragmatic and justifiable approach for use within retrospective and prospective risk assessment.
161 citations
Authors
Showing all 79 results
Name | H-index | Papers | Citations |
---|---|---|---|
Wim De Coen | 47 | 110 | 5880 |
David R. Bell | 27 | 73 | 2119 |
Tomas Öberg | 24 | 94 | 2712 |
Jarkko Loikkanen | 18 | 29 | 733 |
Tomasz Sobanski | 13 | 21 | 861 |
Christoph M. Rheinberger | 12 | 33 | 653 |
Nikolaos Georgiadis | 9 | 17 | 428 |
T. I. Netzeva | 9 | 10 | 433 |
Carmen Estevan | 8 | 15 | 219 |
Ingrid Langezaal | 7 | 10 | 156 |
Derek Knight | 7 | 9 | 875 |
Rupert Simon | 7 | 7 | 546 |
Andrea Gissi | 6 | 10 | 105 |
Kirsi Myöhänen | 6 | 7 | 99 |
Jose V. Tarazona | 6 | 7 | 131 |